Inhibitory effect of l-mimosine on bleomycin-induced pulmonary fibrosis in rats: Role of eIF3a and p27.

Abstract

It has also been shown that the decreased expression of eukaryotic translation initiation factor 3a (eIF3a) by L-mimosine caused cell cycle arrest. Our previous study has found that eIF3a is involved in bleomycin-induced pulmonary fibrosis. Whether the eIF3a/p27 signal pathway is involved in the inhibitory effect of L-mimosine on bleomycin-induced pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of eIF3a, p27, α-SMA, collagen I and collagen III was analyzed by qPCR and Western blot. In vivo, L-mimosine treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of eIF3a, α-SMA, collagen I and collagen III (both mRNA and protein) and expression down- regulation of p27. In vitro, L-mimosine remarkably attenuated proliferation of pulmonary fibroblasts and expression of α-SMA, collagen I and collagen III induced by TGF-β1, and this inhibitory effect of L-mimosine was accompanied by inhibiting eIF3a expression and increasing p27 expression. Knockdown of eIF3a gene expression reversed TGF-β1-induced proliferation of fibroblasts, down-regulation of p27 expression and up-regulation of α-SMA, collagen I, and collagen III expression. These results suggest that L-mimosine inhibited the progression of bleomycin-induced pulmonary fibrosis in rats via the eIF3a/p27 pathway.